Roger A. Marinchak

Effect of Antiarrhythmic Drugs on Defibrillation Threshold: Case Report of an Adverse Effect of Mexiletine and Review of the Literature

Antiarrhythmic agents can influence defibrillation threshold (DFT). Basic research suggests that some class I drugs may have deleterious ejects by raising defibrillation energy requirements. Evaluation of this problem in man has been limited to reports of patients who were more difficult to cardiovert or defibrillate after treatment with amiodarone and class IC agents. In the present report, mexiletine appeared to be the probable cause of an important elevation of DFT in a patient undergoing replacement of a malfunctioning automatic implantable cardioverter/defibrillator [AICD]. This report and the accompanying literature review suggest that more information at both the basic and clinical levels is required. Retesting of device efficacy in terminating induced arrhythmia in the laboratory appears prudent in patients who require antiarrhythmic drug therapy subsequent to AICD implantation.

Effectiveness of propranolol added to a type I antiarrhythmic agent for sustained ventricular tachycardia secondary to coronary artery disease

The effect of adding propranolol to procainamide, quinidine, propafenone or disopyramide was prospectively evaluated in 37 patients, all with prior infarction and inducible ventricular tachycardia (VT). After showing that VT remained inducible during therapy with a type I drug, 23 patients received intravenous propranolol. The ventricular effective refractory period, prolonged by the type I agent, was further increased by propranolol. The cycle length of the VT also increased after the type I drug and propranolol exaggerated this effect. Seven of the 23 patients were rendered noninducible after propranolol and another 10 manifested a greater than 100 ms increase in induced VT cycle length. In the other 14 patients, propranolol was infused immediately after the basal study. If VT remained inducible, testing was repeated after a type I drug was added. The ventricular effective refractory period, as well as the VT cycle length, increased after propranolol and was further prolonged after the addition of a type I agent. Seven of these 14 patients were rendered noninducible, 3 with propranolol alone and 4 others with the combination, and in 4, the VT cycle length was prolonged by greater than 100 ms. A total of 17 patients were discharged on either propranolol alone (3 patients) or on an effective combination (14 patients). During a mean follow-up of 20 months, 1 patient died suddenly, 2 had recurrence of well-tolerated VT and 9 remain on therapy. Thus, propranolol has a demonstrable antiarrhythmic effect in the invasive laboratory and may supplement the antiarrhythmic efficacy of conventional type I antiarrhythmic drugs.

Propafenone for malignant ventricular arrhythmia: An analysis of the literature

Abstract The Food and Drug Administration recently granted approval for the marketing of propafenone (trade name Rythmol), a new class I antiarrhythmic drug, for the treatment of patients with life-threatening ventricular arrhythmias. Although propafenone has been tested in long-term clinical trials in the United States since 1981, many potential prescribing physicians are not familiar with the drug, especially for its labeled use. In addition, no individual published experience has incorporated enough patients to draw firm conclusions regarding the efficacy of the drug for its approved indication. The purpose of this article is to report the results of our review of the literature regarding the usefulness of propafenone in the treatment of these most serious ventricular arrhythmias.

Relationship of delayed depolarization to the QT interval after acute myocardial infarction

The relationship between conduction delay, as manifested by a prolonged QRS or late potentials (LP) detected by signal averaging, and QT prolongation was analyzed in six patients who had QTc greater than or equal to 0.42 second within 48 hours of acute myocardial infarction (AMI). Total QRS, LP, QT, and QTc durations were measured on days 2 to 3, 4 to 5, 6 to 7, and 8-9. In each recording period, the QT interval and QTc interval did not correlate with the QRS duration and LP duration (r less than or equal to 0.52 for each comparison). In 19 out of 27 instances, a sequential change in QT or QTc intervals was discordant with changes in QRS duration and/or LP, i.e., temporal changes in QT intervals were not determined by conduction. Thus, QT prolongation after AMI is not primarily due to regional slowing of conduction that results in regional delays in termination of some action potentials. Global prolongation of repolarization would seem to result from dispersion of action potential duration, not onset.

Acute electrophysiologic effects and antiarrhythmic/antifibrillatory activity of intravenous amiodarone in a chronic feline infarction model

In animal studies, amiodarone has substantial and immediate antiarrhythmic/antifibrillatory action during acute myocardial ischemia. The magnitude of this effect is discordant with the minor degree of prolongation of ventricular action potential duration (APD) and refractoriness which occurs immediately after acute drug administration. However, amiodarones early onset of antiadrenergic activity and inhibition of inward slow calcium channel currents may be important when arrhythmogenesis is dependent on increased sympathetic tone. Because ventricular arrhythmia substrate may differ in acute and chronic ischemic heart disease, we investigated the acute electrophysiologic and antiarrhythmic/antifibrillatory effects of intravenously (i.v.) administered amiodarone in nine chronically infarcted cats. Amiodarone caused significant decreases (−17%) in mean heart rate (HR) and increases (+10%) in mean ventricular effective refractory period (ERP), which occurred promptly after drug administration. Increases in mean ventricular fibrillation (VF) threshold also occurred (11 ± 3.4 and 12.5 ± 2.4 mA for right and left ventricular sites before drug as compared with 45.5 ± 13.2 and 42 ± 13.9 mA after drug). Despite these changes, no significant reduction in the incidence of malignant ventricular arrhythmias induced by programmed stimulation was noted (63% of animals with arrhythmia induced before drug were still inducible after drug). In addition, no change in the increased degree of mean dispersion of refractoriness between infarcted and normal myocardial sites occurred following amiodarone (22.8 ± 3.9 ms before vs. 30.2 ± 2.5 ms after drug). In chronic myocardial infarction without superimposed acute ischemia, early onset of amiodarones antiadrenergic and calcium channel blocking activities may play only a minor role in preventing ventricular arrhythmias inducible by programmed stimulation. More important, mechanisms other than increased sympathetic tone may mediate arrhythmia development in chronic infarction. However, these mechanisms may still be ultimately favorably modified by slower onset of amiodarones other electrophysiologic effects, such as classes I and III activities.

Electrophysiology of beta blockers in supraventricular arrhythmias

beta-adrenergic blocking agents are efficacious in the treatment of patients with a variety of supraventricular tachycardias, based directly on their capacity to counter the effects of beta-adrenergic stimulation on sinus and atrioventricular nodal tissue. Specifically, beta blockers depress sinus node automaticity and inhibit atrioventricular nodal function by prolonging refractoriness and slowing conduction. Supraventricular arrhythmias that depend on these structures either for perpetuation or for conduction to the ventricles are predictably sensitive to beta blockade. These arrhythmias include sinus tachycardia, sinoatrial reentrant, atrioventricular nodal reentrant (dual pathway) and atrioventricular reciprocating (concealed bypass tract) tachycardias, as well as atrial flutter and fibrillation. beta blockers may also be used, in selected patients, to inhibit catecholamine-facilitated accessory pathway function by prolonging refractoriness. beta blockers offer particular clinical advantages, including an acceptable side-effect profile, titratable effect, varied pharmacology and reasonable concordance between efficacy of parenteral and oral dosage forms. The key element in the most effective use of these drugs appears to be an accurate arrhythmia diagnosis that allows for the most appropriate application of a reliable treatment form.

The Cardiac Arrhythmia Suppression Trial: How Has it Impacted on Contemporary Arrhythmia Management?

Implications of the Cardiac Arrhythmia Suppression Trial. A most important issue in cardiology practice has been when and how to treat asymptomatic patients with ventricular arrhythmia. This is a particularly thorny problem, since the presence of complex ventricular ectopy is an independent risk variable in patients with a variety of forms of heart disease. The Cardiac Arrhythmia Suppression Trial (CAST) was designed to answer the question of whether or not abolition of ventricular premature depolarizations, in those who had had a myocardial infarction, would confer any substantial benefit, especially in terms of a mortality reduction. Unfortunately, that question has not yet been answered, but the preliminary results of the CAST has had a major impact on physicians, patients, the scientific community, industry, and regulatory agencies. This article reviews the implications of the CAST and describe how it has affected the contemporary management of patients with cardiac arrhythmia. (J Cardiovasc Electrophysiol, Vol. 1, pp. 457–463, October 1990)

Role of Permanent Pacemakers in the Pharmacologic Therapy of Patients with Reentrant Tachyarrhythmias

Improved pacemaker technology has permitted application in more diverse groups of patients. A more recently described subset appears to be those with reentrant tachycardias treatable with antiarrhythmic drugs. Here, pacing offers the ability both to test the efficacy of a drug regimen and to provide adjunctive fail-safe therapy for those with episodic breakthrough. With the advent of more sophisticated devices, especially those with cardioversion/defibrillation capability, we anticipate a growing interest in these applications which will undoubtedly benefit patients.

Clinical Management of Patients with Nonsustained Ventricular Tachycardia: What Do We Really Know?

The management of patients with nonsustained ventricular tachycardia remains one of the most difficult tasks facing the practicing cardiologist. This common arrhythmia is a marker for death and morbid events in patients with a variety of forms of heart disease, but there is as yet no conclusive evidence that its suppression confers benefit. This paper will review the methods now available to risk stratify patients who have repetitive forms on electrocardiographic monitoring, their advantages and limitations. We will also review some of the trials which have attempted to prove that arrhythmia suppression improves survival. Finally, we will try to provide some recommendations to the clinician, based on what we know about this common arrhythmia. Though we will concentrate our attention on ischemic heart disease, we will briefly discuss the preferred management of patients with other forms of heart disease in whom the presence of nonsustained ventricular tachycardia has prognostic significance. We would like to emphasize that this is a rapidly changing field, and that treatment approaches will necessarily change, based on the results of ongoing clinical trials. The physician must not rigidly adhere to any treatment policy, but rather alter his or her approach based on the development of new information.

The case for explantation of the automatic implantable cardioverter-defibrillator

Abstract We cared for a patient whose malignant ventricular arrhythmia improved as a result of a remission of the underlying cardiac disease. Based on a thorough re-evaluation, we recommended not replacing her pulse generator after battery depletion. This case illustrates the importance of periodic re-evaluation of the need for device therapy.